The Movement Disorder Society revised version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts 2 and 3 reflect patient-reported functional impact and clinician-reported severity of motor signs of Parkinson's disease (PD), respectively. Total scores are common clinical outcomes but may obscure important time-based changes in items. We aim to analyze longitudinal disease progression based on MDS-UPRDS parts 2 and 3 item-level responses over time and as functions of Hoehn Yahr (HY) stages 1 and 2 for subjects with early PD. The longitudinal item response theory (IRT) modeling is a novel statistical method addressing limitations in traditional linear regression approaches, such as ignoring varying item sensitivities and the sum score balancing out improvements and declines. We utilized a harmonized dataset consisting of six studies with 3573 subjects with early PD and 14,904 visits, and mean follow-up time of 2.5 years (+/- 1.57). We applied both a unidimensional (each part separately) and multidimensional (both parts combined) longitudinal IRT models. We assessed the progression rates for both parts, anchored to baseline HY stages 1 and 2. Both the uni- and multidimensional longitudinal IRT models indicate significant worsening time effects in both parts 2 and 3. Baseline HY stage 2 was associated with significantly higher baseline severities, but slower progression rates in both parts, as compared with stage 1. Patients with baseline HY stage 1 demonstrated slower progression in part 2 severity compared to part 3, whereas patients with baseline HY stage 2 progressed faster in part 2 than part 3. The multidimensional model had a superior fit compared to the unidimensional models and it had excellent model performance.
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